Serum Alkaline Phosphatase Activity Research Articles

Preclinical evaluation of the efficacy and safety of AAV8-TNAP-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia.

We previously documented successful resolution of skeletal and dental disease in the infantile and late-onset murine models of hypophosphatasia (HPP), with a single injection of an adeno-associated serotype 8 vector encoding mineral-targeted TNAP (AAV8-TNAP-D10). Here, we conducted dosing studies in both HPP mouse models. A single escalating dose from 4x108 up to 4x1010 (vg/b) was intramuscularly injected into 4-day-old Alpl-/- mice (an infantile HPP model) and a single dose from 4x106 up to 4x109 (vg/b) was administered to 8-week-old AlplPrx1/Prx1 mice (a late-onset HPP model). Wild-type littermates were used as controls. Serum alkaline phosphatase activity was increased, and PPi levels were decreased in a dose-dependent manner in both the Alpl-/- and AlplPrx1/Prx1 models. Radiographic and μCT analysis of long bones of female and male Alpl-/- mice showed full correction of skeletal phenotype at 4x1010 vg/b. We observed full correction of the bone phenotype at 4x108 and 4x109 in female AlplPrx1/Prx1 mice, but bones remained hypomineralized with the 4x106 and 4x107 (vg/b) doses after 70days of treatment. We observed skeletal improvements using the 4x109 (vg/b) dose, but the phenotype was not fully corrected in male AlplPrx1/Prx1. Immunohistochemistry using anti-TNAP and anti-D10 antibodies showed high immunolocalization in the femurs of female AlplPrx1/Prx1 mice, while D10 immunolocalization was high in the liver of male AlplPrx1/Prx1 mice at a dose of 4x109 (vg/b). This sex-dependent difference was not seen in the infantile HPP model. A serum proteome analysis showed enhanced inflammatory pathways in treated AlplPrx1/Prx1 males compared to treated female mice. We also found a few areas of ectopic calcification in soft organs at the highest tested dose of 4x1010 (vg/b) in Alpl-/- or 4x109 (vg/b) in the AlplPrx1/Prx1 model. This pre-clinical study will inform the design of clinical trials to develop gene therapy in early-onset and late-onset HPP patients.

Development of Paget's disease of bone in adults inheriting SQSTM1 mutations: a long-term follow-up.

In a 2015 study of SQSTM1 mutation carriers who had initial negative bone scintigraphy, we found that the rate of development of Paget's disease of bone (PDB) over 5yr was low. We report here an additional 8-yr follow-up of this cohort, exploring the hypothesis that the rate of development of PDB would increase as the cohort aged. In the current study, 21 of 24 subjects from 2015 who had a negative bone scintiscan at baseline and at first follow-up, had a repeat scintiscan and measurement of total serum alkaline phosphatase activity. Two subjects with P392L mutations were identified as having PDB (monostotic in one case, 2 bones involved in the other), giving an incidence during this follow-up period of 1 per 87 patient years or 11.9 per 1000 patient years. This was contrary to our hypothesis, as the rate of development had decreased as the cohort aged. When we compared by survival analysis the age at presentation with symptomatic PDB in the older generation, we found that the age of onset was later and disease severity in the affected relatives was markedly less than in their clinically affected parents (p< .001). Our results are in keeping with other recently published studies and the general secular trend in PDB and support the idea that an important environmental-genetic interaction is involved with the development of PDB and that exposure to the putative environmental factor has substantially reduced.

Pretreatment administration of hydro-ethanolic extract of Syzygium aromaticum prevents thioacetamide-induced liver injury in rat

IntroductionLiver injury is an important problem in healthcare. Thioacetamide (TAA)-induced liver injury is an established model in experimental research for assessing the impact of various toxins and pharmaceuticals on the liver. TAA induces its harmful effects by the production of oxidative biomolecules. Oxidative stress subsequently alters liver function, resulting in alterations in the enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Syzygium aromaticum has significant antioxidant and anti-inflammatory properties and has been utilised in traditional medicine for liver diseases. Therefore, this study evaluated the hepatoprotective effect of the hydro-ethanolic extract of Syzygium aromaticum (HESA) against TAA-induced liver injury.Material and methodsHepatotoxicity was induced with intraperitoneal administration of TAA (150 mg/kg body weight, 3 days per week for 4 weeks) in Wistar rats. The pretreatment with HESA was conducted at three doses of 50, 150, and 300 mg/kg body weight, administered orally, starting 4 weeks before TAA administration and continued for 8 weeks. The activities of serum AST, ALT, and ALP, as well as liver superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and malondialdehyde (MDA), were assessed. Histopathological analyses were conducted using hematoxylin and eosin (H&E) staining.ResultsThe findings showed that HESA pretreatment significantly lowered TAA-induced oxidative stress. Additionally, TAA significantly increased AST, ALT, and ALP serum levels, whereas HESA significantly recovered the corresponding values. H&E staining also showed that TAA-induced structural liver damage was characterised by central vein dilatation, and necrosis, and apoptosis in adjacent cells. The histopathological findings of the TAA group were partially recovered in the pretreatment extract groups.ConclusionThe results of this study support the antioxidant and anti-inflammatory properties of Syzygium aromaticum against TAA-induced liver injury.

Effects of Bacillus subtilis KG109 on Growth Performance, Carcass Quality, Serum Indicators, Intestinal Morphology, and Digestive Enzymes in Broilers.

The purpose of this experiment is to investigate how different doses of Bacillus subtilis KG109 powder affect the growth performance, carcass quality, serum biochemical indexes, serum antioxidant and immunological index, intestinal morphology, and digestive enzyme activity of broilers. Four hundred chicks of a similar weight (1 day old) are randomly assigned to four groups of five replicates of 20 chicks each (half males and half females). The control group is fed a basal ration, and the experimental groups T1, T2, and T3 are supplemented with 6.0 × 108 CFU/kg, 1.2 × 109 CFU/kg, and 1.8 × 109 CFU/kg of Bacillus subtilis KG109 bacterial powder, respectively, in the basal ration. The feeding cycle is 52 d. Compared with the control group, Bacillus subtilis KG109 powder (1) increases the broiler feed conversion ratio (FCR) (p < 0.05), (2) improves the carcass quality (slaughter rate, cooking loss, L* and b* values) (p < 0.05), (3) enhances the serum biochemical indexes (alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), albumin (ALB), and triglycerides (TG)) (p < 0.05), (4) improves the serum antioxidant capacity (total an-tioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-PX)) and immunoglobulins (lg A, lg G, lg M) (p < 0.05), (5) improves the intestinal morphology (villus height and villus height to crypt depth (VCR)) (p < 0.05), and (6) increases the intestinal digestive enzyme activities (amylase, protease, and lipase) (p < 0.05). In summary, adding Bacillus subtilis KG109 to broiler diets can result in a significant decrease in broilers' FCR, an increase in their slaughtering rate, a decrease in their serum ALT, ALP, and AST activities, an increase in their serum TG content, an improvement of their immune and antioxidant capacity, an improvement of their intestinal morphology, and an improvement of their intestinal digestive enzyme activity. It is recommended to add 1.8 × 109 CFU/kg of bacteria.

Biochemical perturbations associated with Salmonella gallinarum infection in laying hens:Is oxidative stress implicated?

The aim of this study was to investigate some biochemical and tissue changes associated with Salmonella gallinarum infection in laying hens (LHs), and the complicities of oxidative stress (OS). Fifty LHs were assigned to two groups of 25 LHs infected with S. gallinarum (109 cfu*mL-1 of S. gallinarum) and 25 uninfected controls. Biochemical assays and histopathology were carried out following standard procedures. There was a significant loss of body weight, drop in egg production, as well as 28% mortality in the infected group. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and superoxide dismutase (SOD) activities, as well as serum total protein, globulin, total cholesterol, total bilirubin, uric acid, creatinine and malondialdehyde (MDA) levels were significantly higher, whereas serum albumin levels were significantly lower in infected LHs. There were inflammatory, degenerative and necrotic changes observed in the affected organs. Considering the significant elevation in MDA levels coupled with elevated SOD activity in the infected LHs, OS may play a significant role in the pathology of fowl typhoid and may suggest a possible treatment of infected layers with antioxidants.

A Multi-Enzyme Complex That Mitigates Hepatotoxicity, Improves Egg Production and Quality, and Enhances Gut and Liver Health in Laying Hens Exposed to Trace Aflatoxin B1.

Aflatoxin B1 is a prevalent secondary hazardous metabolite generated by fungus present in feed ingredients and the surrounding environment: enzymes are currently being recognized as an efficient and promising approach to reducing the associated risks. The objective of this study was to assess the effects of varying doses of enzyme complexes on several parameters in laying hens that were exposed to aflatoxin. During an 8-week experiment, a total of 288 Yukou Jingfen No.6 laying hens were placed into four groups. These groups included a group treated with toxins (CON group) and groups supplemented with compound enzyme complexes at doses of 250 g/t (E1 group), 500 g/t (E2 group), and 1000 g/t (E3 group). The E2 and E3 groups exhibited a statistically significant 2.6% increase in egg production rate compared to the CON group (p < 0.05). In addition, the E2 group showed significant improvements in both the feed-to-egg ratio and egg weight (p < 0.05). In addition, the E2 and E3 groups showed improved hutch unit and egg white height compared to the control group (p < 0.05). The E2 and E3 groups showed a substantial rise in liver health indicators, namely serum alanine transaminase (ALT) and alkaline phosphatase (ALP) activity. On the other hand, malondialdehyde (MDA) was lowered, and total superoxide dismutase (T-SOD) and total antioxidant capacity (T-AOC) were raised. These findings were statistically significant (p < 0.05). The E2 and E3 groups showed notable enhancements in intestinal morphology, as evidenced by a rise in villus height and a decrease in crypt depth in all segments of the intestine (p < 0.05). Furthermore, analysis of 16S rRNA sequencing revealed that these participants had a higher prevalence and variety of microorganisms in their gut microbiota. More precisely, there was a significant rise in the abundance of Bacteroidota and a decline in Firmicutes at the level of the phylum. In general, the inclusion of the enzyme complex had advantageous impacts on performance, egg quality, intestinal morphology, intestinal barrier function, and intestinal flora in laying hens. Our results indicate that toxin-degrading enzymes, when used as feed additives, play a significant role in mitigating AFB1 contamination in diets and improving the production performance of laying hens.

Study on the mechanism of Fuzheng Huayu formula against biliary fibrosis in mice

Objective: To investigate the effect and mechanisms of Fuzheng huayu formula (FZHY) on biliary fibrosis in mice. Methods: Mdr2 gene knowout (Mdr2-/-) mice were randomly divided into model group, FZHY-treated group and obeticholic acid (OCA)-treated group. Wide type C57BL/6J (WT) mice of the same age were used as the control group. Mdr2-/- mice were treated with the corresponding drugs by gavage from the first day of the 9th week old. The WT and model groups were given 0.3% sodium carboxymethyl cellulose by gavage, and the mice were sacrificed at the end of 12th week old. The activities of serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were detected by high-speed biochemical analyzer. H&E staining and sirius red staining were used to observe the pathological changes of liver tissues. The hepatic hydroxyproline content was determined. The hepatic expressions of Col-Ⅰ and α-SMA, ductular reaction markers Epcam, CK7, CK19, and the expression of Pcna, Mki67 and Ccnd1; as well as the expression of inflammatory cytokines Ccl2, Ccl5, Tnf-α, Il10 and Cxcl4 were detected by immunohistochemical staining, western blot and qRT-PCR, respectively. Furthermore, the expression of PPARα and the phosphorylation NF-κB were detected by western blot. Results: Compared with WT mice, the serum ALT and ALP activities of Mdr2-/- mice were significantly increased (P<0.001). The percentage of SR positive stained area and hepatic Hyp content were significantly increased (P<0.01). The hepatic expression of Col-Ⅰ and α-SMA; Epcam, CK7, CK19, Pcna, Mki67 and Ccnd1; Ccl2, Ccl5, Tnf-α, Il10 and Cxcl4 were significantly increased (P<0.01). However, both FZHY and OCA significantly reversed the elevation of these aforementioned indicators (P<0.05; P<0.01). Further study showed that the hepatic expression of PPARα in Mdr2-/- mice was significantly lower than that of WT mice, however the phosphorylation of NF-κB was significantly enhanced (P<0.01). The expression of PPARα in liver tissues of FZHY mice was significantly increased (P<0.05), and the NF-κB phosphorylation was significantly inhibited compared with Mdr2-/- mice (P<0.05). Conclusion: FZHY significantly ameliorated liver fibrosis, ductular reaction and inflammation in Mdr2-/- spontaneous biliary fibrosis mice, and its mechanism was related to the regulation of PPARα/NF-κB pathway.

Prognostic Impact of a Histologic Grading Scheme in Dogs Diagnosed With Rib Chondrosarcoma.

Data regarding the outcome of canine rib chondrosarcoma is sparse and varied. While grade of tumour is associated with outcome for canine appendicular chondrosarcoma, the association of grade with outcome for canine rib chondrosarcoma is unclear. This study aimed to correlate the grade of canine rib chondrosarcoma with median survival time. Retrospectively, cases of primary rib chondrosarcoma were identified, and tumours were graded based on a 3-tier adapted human grading scheme. Twenty-two patients were included in the survival analysis. The median survival time was 1427 days (range: 27-3354 days). This was not significantly different for patients with grade I versus II versus III (p = 0.82), grade I-II versus III (p = 0.34), or grade I versus II-III (p = 0.49). No variables assessed including age, weight, tumour location (cranial vs. caudal thorax; left vs. right hemithorax), tumour location on rib (proximal, middle, and distal), radiographic appearance (lytic, proliferative, or mixed), elevated serum alkaline phosphatase activity, grade, grade specific histologic features (matrix production, architecture, pleomorphism, cellularity, necrosis, and total score), adjunct therapy post-surgical excision, development of metastatic disease post-surgery, or local recurrence post-surgery were found to impact the risk of death due to chondrosarcoma. In this limited group of patients, the grading scheme reported here, and the other variables assessed did not appear to offer additional prognostic information. However, this data must be interpreted considering the small sample size and thus low statistical power. Additional studies are needed to determine the true impact of grade on outcome for canine rib chondrosarcomas.

Advanced chelate technology-based trace minerals reduce inflammation and oxidative stress in Eimeria-infected broilers by modulating NF-kB and Nrf2 pathways

This study investigated the effects of substituting inorganic trace minerals (ITM) with advanced chelate technology-based TM (ACTM) in broiler chicken feed on productive performance, metabolic profile, humoral immunity, antioxidant status, and modulation of NF-kB and Nrf2 signaling pathways in mixed Eimeria species exposure. The study involved 480 newly hatched male broiler chickens, which were divided into 5 treatment groups, each with 6 replicate cages and 16 chickens per replicate. The experimental treatments included an uninfected negative control group fed a basal diet with recommended inorganic TM levels (NC), an infected positive control group fed the same diet (PC), a PC group supplemented with salinomycin (SAL), and two PC groups in which the basal diet was replaced with 50% and 100% ACTM instead of inorganic TM (ACTM50 and ACTM100, respectively). All groups, except for the NC group, were orally challenged with mixed Eimeria species oocysts on day 14. According to the results, the PC group showed lower feed intake, breast yield, low-density lipoprotein-cholesterol concentration, lactobacillus spp. counts, and serum IgG levels, but higher jejunal TGF-β expression versus the NC group. The broilers in the NC, SAL, and ACTM100 groups showed higher body weight gain, carcass yield, and TGF-β expression, but lower serum alkaline phosphatase activity, ileal E. coli count, and jejunal expression levels of IL-1β, IL-6, IFN-γ, Nrf2, and SOD1 compared to the PC group, with the NC group having the highest body weight gain and lowest IL-1β and Nrf2 expression levels. Furthermore, the administration of ACTM100 treatment improved feed efficiency, increased serum iron, zinc, manganese, and copper levels, enhanced total antioxidant capacity and different antioxidant enzyme activities, and reduced malondialdehyde concentration. In conclusion, complete replacement of ITM with ACTM effectively protects broilers from Eimeria infection, with similar positive effects to SAL treatment in terms of productive performance and anti-inflammatory responses and better antioxidant responses and mineral availability.

7944 Elevated Serum Alkaline Phosphatase without other Abnormalities of Liver Associated Enzymes as an early Indicator of Glucose Intolerance: A Case Series

Abstract Disclosure: B.K. Bowens: None. C. Godar: None. D. LaChance: None. T.D. Hoang: None. M.K. Shakir: None. Glucose intolerance (GI) is defined as dysglycemia and includes impaired fasting glucose, impaired glucose tolerance, and prediabetes. Early detection of GI could lead to appropriate treatment and delay the progression to diabetes mellitus. The cases below detail two patients with elevated serum alkaline phosphatase (ALP) without other liver-associated enzyme abnormalities as an early indicator of GI. Case 1: A 54-year-old woman with a history of multinodular goiter status post thyroidectomy (2020), adrenal incidentaloma (2016), and asthma was incidentally found to have an elevated HbA1C (A1C) of 6.3% on screening labs in 2015. At that time, her ALP was 73 IU/L (ref 44−121). Her ALP levels slowly rose from 88 to 152 IU/L by September 2020. Work up did not reveal any etiological factors for the elevated ALP. One month later, HbA1C was found to be 7.6%. Metformin was initiated with improvement in A1C to 6.3% with an ALP of 130 IU/L. However, metformin was discontinued due to intolerance. In April 2023, her A1C was 9.3% with an ALP of 134 IU/L. A1C rose to 12.8% in Jun 2023 at which time she was started on insulin glargine, insulin aspart, sitagliptin, and was restarted on metformin. Her A1C decreased to 8.6% in August 2023 with normalization of ALP to 88 IU/L. Case 2: A 53-year-old woman with a history of hypertension, hyperlipidemia, obstructive sleep apnea, and non-ischemic cardiomyopathy in 2004 was found to have an elevated A1C of 5.8% on her screening labs in Jun 2019. Her ALP was notably in the high-normal range until Oct 2021 when it was found to be 138 IU/L. Her most recent A1C was 5.9% with an ALP of 142 IU/L. The patient was started on semaglutide (WegovyTM) briefly but was unable to tolerate the side effects. She was then started on metformin 500mg BID and dulaglutide with normalized ALP level. Discussion: Emerging evidence has shown that serum ALP activity is modestly increased in cardiometabolic diseases such as type 2 diabetes, dyslipidemia, hypertension, and peripheral arterial disease. These are increasingly being considered as inflammatory disorders and it has been shown that serum ALP level was positively and independently associated with metabolic syndrome both in men and women. It is possible that ALP could be an indicator of non-alcoholic fatty liver disease (NAFLD) which is associated with GI. Typically, NAFLD presents with higher ALT and GGT, however, occasionally isolated enzyme elevations or no elevated enzymes at all may occur. Conclusion: These cases suggest that an isolated elevation in ALP could be indicative of GI. Patients incidentally found to have an elevated ALP should be worked up further for possible evidence of GI. Early detection of GI could delay progression to diabetes and decrease morbidity. Presentation: 6/1/2024

Association between Mixed Heavy Metal Exposure and Arterial Stiffness, with Alkaline Phosphatase Identified as a Mediator.

Elevated arterial stiffness has been associated with exposure to heavy metals such as lead (Pb) and cadmium (Cd). However, the collective impact of multiple metals and the underlying mechanisms are not fully elucidated. The purpose of this study was to assess the combined effects of exposure to nine heavy metals on arterial stiffness and explore whether serum alkaline phosphatase (ALP) acts as a mediator in this relationship. In the retrospective analysis, data from 8,700 participants were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Arterial stiffness was measured by estimated pulse wave velocity (ePWV). The cumulative impact of exposure to multiple metals was examined using adaptive elastic-net, environmental risk score, weighted quantile sum regression, and quantile g-computation. Additionally, mediation analysis was conducted to explore the potential mediating role of serum ALP. We found that combined exposure to multiple metals was consistently associated with elevated ePWV, with Ba, Pb, and Sb exhibiting the greatest contributions. Notably, serum ALP partially mediated the associations between individual (Pb, Sb) and mixed metal exposure with ePWV, with mediation proportions at 10.76% for Pb, 18.22% for Sb, and 11.07% for mixed metal exposure. In conclusion, this study demonstrates a clear association between exposure to heavy metals, either individually or in combination, and heightened arterial stiffness. Furthermore, the findings suggest that serum ALP activity may act as a mediator in these relationships.

Evaluation of growth, antioxidant status, hepatic enzymes and immunity of Nanoselenium-Fed Cirrhinus mrigala.

This study was conducted to investigate the effects of selenium nanoparticle (Se-NP) supplementation on the growth performance, carcass composition, antioxidant status, hepatic enzyme activities, and immunity of Cirrhinus mrigala. For this purpose, fish with an average initial weight of 7.44 ± 0.04 g were fed five experimental diets containing 0 (control), 0.25, 0.5, 1, and 2 mg kg-1 Se-NPs diets for 90 days. The analysed selenium (Se) contents of the diets were 0.35, 0.64, 0.92, 1.43, and 2.39 mg kg-1. Twenty five fish were randomly distributed in each of 5 aquarium (36 × 23.7 × 24.3 inches) in triplicate. The results showed that supplementation with Se up to 0.92 mg/kg significantly increased (p<0.05) weight gain, weight gain% (WG%), and specific growth rate (SGR) by 34%, 33%, and 16%, respectively, compared to the control diet. Dietary Se concentrations up to 0.92 mg/kg significantly increased the crude protein and crude fat and reduced (p<0.05) the moisture content as compared to the control group. Fish fed 0.92 mg kg-1 Se had significantly lower malondialdehyde (MDA) contents and higher activities of catalase, superoxide dismutase, and glutathione peroxidase in liver and serum as compared to other experimental diets. Moreover, a significant increase (p<0.05) in the level of serum immunoglobulin and lysozyme (LYZ) activity was recorded in fish fed 0.92 mg/kg Se diet. Moreover, the highest (p<0.05) values of aspartate transaminase (AST) and alanine transaminase (ALT) were recorded in fish fed 2.39 mg/kg Se level. However, serum alkaline phosphatase (ALP) activity remained unaffected by dietary treatment. Broken-line regression analysis indicated that 0.83 mg/kg Se is required for the optimum growth performance of C. mrigala.

Effects of dietary puerarin on growth, digestive enzyme, antioxidant capacity, immune and liver health of Acanthopagrus latus

This study was conducted to investigate the effects of puerarin on growth, digestive enzymes, antioxidant capacity, immunity and liver health of Acanthopagrus latus. Four diets were formulated: a control diet (C) and C supplemented with 200, 400, and 600 mg/kg puerarin (CP2, CP4, and CP6, respectively) and a eight-week feeding trial was conducted of fish. The results showed that the addition of 400 mg/kg puerarin significantly increased weight gain (WG), specific growth rate (SGR), and decreased the feed conversion ratio (FCR) compared to C group. Dietary supplementation with 600 mg/kg puerarin significantly increased lipase (LPS) activity compared to the C group. The addition of 200 mg/kg puerarin significantly reduced low-density lipoprotein cholesterol (LDL-C) and 400 mg/kg puerarin significantly reduced total cholesterol (T-CHO), triglycerides (TG) and HDL-C compared to the C group. Dietary supplementation with 400 mg/kg puerarin significantly increased serum and liver glutathione (GSH) activity and decreased malondialdehyde (MDA) content compared to the C group. Addition of 400 mg/kg puerarin significantly increased liver catalase (CAT) activity compared to the C group. Supplementation of 600 mg/kg and 400 mg/kg of puerarin significantly increased serum alkaline phosphatase (AKP) and lysozyme (LZM) activities, respectively. Compared to the C group, the addition of 200 mg/kg of puerarin significantly increased the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) in the liver. CP4-feeding significantly upregulated the expression of nrf2, ho-1, and gclc while downregulating the expression of keap1 compared to the C group. The addition of puerarin significantly reduced the expression of tnf-α and il-6 compared to the C group. Supplementation of 200 mg/kg puerarin significantly reduced the expression of bax compared to the C group. In conclusion, dietary supplementation with puerarin had positive effects on the growth, digestive enzymes, antioxidant capacity, immunity, and liver health of fish, particularly at 503.5 mg/kg.

Effectiveness of Hydrated Sodium Calcium Aluminosilicates and Discarded Date Pits as Dietary Adsorbents for Aflatoxin B1 in Enhancing Broiler Chicken Productive Performance, Hepatic Function, and Intestinal Health.

The research aimed to evaluate how effective hydrated sodium calcium aluminosilicates (HSCASs) and discarded date pits (DDPs) are as dietary adsorbents for aflatoxin B1 (AFB1) in enhancing the performance and health of broiler chickens aged 16 to 30 days. A total of 240 Ross 308 straight-run broilers were randomly allocated into four dietary groups, each with 10 replicates: a control diet, a control diet with 1000 ppb AFB1, an AFB1-contaminated diet with 0.5% HSCAS, and an AFB1-contaminated diet with 4% DDP. Incorporating HSCASs or DDPs into the AFB1-contaminated diet resulted in significant improvements across various parameters, involving increased body weight, improved feed conversion ratio, higher dressing percentage, decreased relative weights of kidney and spleen, elevated serum levels of total protein, globulin, and glucose, reduced serum alanine aminotransferase activity, and heightened hepatic protein concentration and glutathione peroxidase activity, along with diminished hepatic malondialdehyde content and glutamic oxaloacetic transaminase activity. Moreover, both supplements led to increased ileal villus height and surface area, enhanced apparent nitrogen-corrected metabolizable energy digestibility, and decreased AFB1 residues in the liver and kidney. Moreover, the dietary inclusion of DDPs significantly decreased relative liver weight, raised serum albumin concentration, lowered serum alkaline phosphatase activity, enhanced hepatic total antioxidant capacity level, and augmented ileal villus width. Conversely, the dietary addition of HSCASs significantly heightened apparent crude protein digestibility. In conclusion, the inclusion of HSCASs and DDPs in AFB1-contaminated diets can mitigate the toxic effects of AFB1 on broiler chickens, with DDPs exhibiting additional advantages in optimizing liver function and gut morphology.

Circulating 25-hydroxycholecalciferol and calcium levels, and alkaline phosphatase activity among people living with and without human immunodeficiency virus and injecting drugs in kenya

Background People who inject drugs (PWID) and living with the human immunodeficiency virus (PLHIV) are at higher risk of suffering marked derangements in micronutrient levels, leading to poor disease and treatment outcomes. Consequently, this can be monitored by measuring key biomarkers, such as total circulating (serum) 25-hydroxycholecalciferol (25(OH)D3), calcium, and alkaline phosphatase (ALP) for timely intervention. Therefore, circulating levels of 25(OH)D3 and calcium, and ALP activity were determined in PWID and are highly active anti-retroviral treatment (HAART)-experienced or -naive, along with those without HIV infection.MethodsThis cross-sectional study compared serum concentrations of 25(OH)D3, calcium, and ALP in Kenyan PLHIV and were HAART-naive (n = 30) or -experienced (n = 61), PWID and without HIV (n = 132).Results Circulating 25(OH)D3 levels were significantly different amongst the study groups (P < 0.001), and were significantly lower in the HAART-experienced (median, 17.3; IQR, 18.3 ng/ml; P < 0.001) and -naive participants (median, 21.7; IQR, 12.8 ng/ml; P = 0.015) relative to uninfected (median, 25.6; IQR, 6.8 ng/ml) PWID. In addition, the proportions of vitamin D deficiency (55.7%, 40.0%, and 17.4%) and insufficiency (31.1%, 53.3%, and 63.6%) compared to sufficiency (13.1%, 6.7%, and 18.9%; P < 0.001) were greater amongst HAART-experienced, -naive, and uninfected study groups, respectively. Likewise, serum total calcium concentrations were lower in the HAART-experienced relative to HIV-negative (P = 0.019) individuals. Serum ALP activity was also lower in the HAART-experienced in contrast to HIV-negative PWID (P = 0.048). Regression analysis indicated that predictors of circulating 25(OH)D3 were: age (β = 0.287; R2 = 8.0%; P = 0.017) and serum ALP (β = 0.283; R2 = 6.4%; P = 0.033) in the HAART-experienced PWID, and serum ALP (β = 0.386; R2 = 14.5%; P < 0.001) in the HIV-negative PWID.Conclusion This study suggests that HIV-1 infection and HAART, including injection substance use, decrease circulating 25(OH)D3, calcium and ALP activity. In addition, age and ALP activity are associated with low circulating vitamin D levels in HAART-experienced PWID. The results highlight the importance of incorporating vitamin D and calcium supplementation in treatment and rehabilitation protocols for PLHIV.

Enzyme replacement therapy for hypophosphatasia-The current paradigm.

Hypophosphatasia (HPP) is a rare, inherited, and systemic disorder characterized by impaired skeletal mineralization and low tissue nonspecific serum alkaline phosphatase (TNSALP) activity. It is caused by either autosomal recessive or dominant-negative mutations in the gene that encodes TNSALP. The phenotype of HPP is very broad including abnormal bone mineralization, disturbances of calcium and phosphate metabolism, pain, recurrent fracture, short stature, respiratory impairment, developmental delay, tooth loss, seizures, and premature death. Other than supportive care, there has been no disease-specific treatment available for those with HPP. Asfotase alfa is a fully humanized, recombinant enzyme replacement therapy for the management of HPP. It is available in several countries for the treatment of the more severe forms of HPP, namely perinatal and infantile HPP. This review will summarize the preclinical data on asfotase alfa and highlight the data from clinical trials and case reports. These data show the transformative nature of asfotase alfa when administered as part of an interdisciplinary treatment model.

Effects of low dietary calcium and lipopolysaccharide challenges on production performance, eggshell quality, and bone metabolism of laying hens.

Dietary calcium supply is essential for bone development and egg production in laying hens. This study investigated the effects of low dietary calcium and lipopolysaccharide (LPS) induced immune challenge in aged laying hens. A total of thirty-two Hy-Line Brown laying hens at 80 weeks old with an average laying rate of 62% were randomly divided into two groups and fed a normal calcium diet (3.57% Ca, NCA) or low calcium diet (2.08% Ca, LCA). At 88 weeks, the experiment was designed using a 2 × 2 factorial arrangement, and hens were intraperitoneally injected with saline (SAL) or LPS (0.5mg/kg, 0.5mg/kg, or 1.5mg/kg body weight) once every 48h intervals over 5 days. Production performance, egg quality, and bone physiology were evaluated. Results showed that LPS challenge decreased the hen-day egg production, egg mass, and eggshell traits (p < 0.05), but increased (p < 0.05) the calcium content of the tibia compared to SAL-injected hens. LCA diet decreased (p < 0.05) the hen-day egg production, and eggshell traits such as weight, percentage, strength, and thickness compared to the NCA diet. LCA diet increased the serum alkaline phosphatase (ALP) activity (p < 0.01) and tibial expression of ALP (p < 0.05) compared to NCA diet. LPS injection suppressed both the serum ALP activity (p < 0.05) and tibial expression of ALP (p < 0.001) compared to SAL injection. Furthermore, LPS injection increased (p < 0.05) the expression of both pro and anti-inflammatory cytokines in the spleen and tibia. The expression of cathepsin K ( Cts K ) and matrix metalloproteinase 9 ( MMP-9 ) were downregulated by LPS injection (p < 0.001). Broken and shell-less egg production and calcium content of eggshell, as well as tibial mRNA expression of osteocalcin ( Ocn ), tumor necrosis factor-alpha ( TNF-α ) and tartrate-resistant acid phosphatase ( TRAP ) were affected by the interaction (p < 0.05) of diet and injection. Therefore, this study demonstrated that to certain extents, low dietary calcium and LPS challenge dysregulated bone homeostasis and metabolism, with detrimental effects on the performance and eggshell quality of aged laying hens.

Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice.

The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown. Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF). Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF. We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.

Cerium oxide nanoparticles display antioxidant and antiapoptotic effects on gamma irradiation-induced hepatotoxicity.

Throughout radiotherapy, radiation of the hepatic tissue leads to damage of the hepatocytes. We designed the current study to examine how cerium oxide nanoparticles (CONPs) modulate gamma irradiation-induced hepatotoxicity in rats. Animals received CONPs (15 mg/kg body weight [BW], ip) single daily dose for 14 days, and they were exposed on the seventh day to a single dose of gamma radiation (6 Gy). Results showed that irradiation increased serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities. Furthermore, it elevated oxidative stress biomarker; malondialdehyde (MDA) and inhibited the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in hepatic tissues homogenate. Additionally, hepatic apoptotic markers; caspase-3 (Casp-3) and Casp-9 were elevated and the B-cell lymphoma-2 (Bcl-2) gene level was decreased in rats exposed to radiation dose. We observed that CONPs can modulate these changes, where CONPs reduced liver enzyme activities, MDA, and apoptotic markers levels, in addition, it elevated antioxidant enzyme activities and Bcl-2 gene levels, as well as improved histopathological changes in the irradiated animals. So our results concluded that CONPs had the ability to act as radioprotector defense against hepatotoxicity resulted during radiotherapy.

Features of post-surgical menopause with concomitant primary hypothyroidism: A prospective single-stage clinical study

Background. In recent decades, the frequency of surgical interventions on reproductive system organs has been steadily increasing. In gynecological practice, preference is given to minimally invasive surgery and precision treatments, especially involving ovaries. Despite the modern approach, it is not always possible to preserve this endocrine organ, which leads to post-surgical menopause (PSM). The relatively high incidence of total hysterectomy-associated PSM and primary hypothyroidism in late reproductive age often leads to their combination. Clinical manifestations aggravating each other form an unfavorable vicious circle. Aim. To study the features of the PSM course with concomitant primary hypothyroidism. Materials and methods. A prospective clinical study included 130 women aged 45 to 55 years with a history of PSM. The main group consisted of 70 patients with PSM with subclinical primary hypothyroidism. A control group included 60 PSM patients without thyroid disorders. We assessed the effect of hypothyroidism on the PSM course by comparing several indicators in the main and control groups. Results. It was found that in the main group patients, severe 26.5% and moderate 38.8% menopausal syndrome prevailed, while in the control group patients, such forms were twice as common. In the women of the main group, the levels of triglycerides were higher than those in the control group by 1.3 times (2.6±0.86 mmol/L and 1.43±0.33 mmol/L, respectively). The total serum alkaline phosphatase activity in patients in the study groups was 29.8% higher than in healthy women. Conclusion. It can be concluded that the severity of menopausal disorders depends on the thyroid status, with more severe in patients of the main group with hypothyroidism. In addition, in patients of the main group with hypothyroidism, dyslipidemia is more pronounced, which predisposes them to severe diseases in the future, in particular cardiovascular disorders, the unfavorable course of metabolic syndrome, and the development of postmenopausal osteoporosis.